title: Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons.
abstract: Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate) Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine food chain causing neurological deficits. To determine the mechanism of CTX-mediated cytotoxicity in human neurons, we measured extracellular lactate dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) and H2AX phosphorylation at serine 139 as a measure for DNA damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P-CTX-3C. We found these marine toxins can induce a time and dose-dependent increase in extracellular LDH activity, with a concomitant decline in intracellular NAD(+) levels and increased DNA damage at the concentration range of 5-200 nM. We also showed that pre- and post-treatment with rosmarinic acid (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can attenuate CTX-mediated neurotoxicity. These results further highlight the potential of RA in the treatment of CTX-induced neurological deficits.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia, n.braidy@unsw.edu.au.
authors.forename: N
authors.initials: N
authors.lastname: Braidy
authors.forename: A
authors.initials: A
authors.lastname: Matin
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Chinain
authors.forename: D
authors.initials: D
authors.lastname: Laurent
authors.forename: G J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D002922:Ciguatoxins / Q000633:toxicity*; D002934:Cinnamates / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D053630:Depsides / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D002922:Ciguatoxins; D002934:Cinnamates; D053630:Depsides; D018696:Neuroprotective Agents; D000097123:Rosmarinic Acid